{PDOC00263}
{PS00291; PRION_1}
{PS00706; PRION_2}
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* Prion protein signatures *
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Prion protein (PrP) [1,2,3] is a  small glycoprotein found in high quantity in
the brains of  humans  or animals  infected  with  a  number  of  degenerative
neurological diseases such as  Kuru, Creutzfeldt-Jacob disease (CJD),  scrapie
or bovine spongiform encephalopathy (BSE).   PrP is encoded in the host genome
and expressed  both  in  normal  and  infected  cells.  It  has  a tendency to
aggregate yielding polymers called rods.

Structurally, PrP is  a  protein consisting  of  a signal peptide, followed by
an N-terminal  domain  that contains tandem repeats of a short motif (PHGGGWGQ
in mammals, PHNPGY in chicken), itself followed  by  a highly conserved domain
of about  140  residues  that  contains a  disulfide bond.  Finally comes a C-
terminal hydrophobic domain post-translationally  removed when PrP is attached
to the extracellular side of the cell membrane by a GPI-anchor.  The structure
of PrP is shown in the following schematic representation:

 +---+----------------+-******-------------------****-----+-----+
 |Sig| Tandem repeats |                    C        C    S|     |
 +---+----------------+--------------------|--------|----|+-----+
                                           +--------+    |
                                                         GPI

'C': conserved cysteine involved in a disulfide bond.
'*': position of the patterns.

As signature pattern for PrP,  we  selected a perfectly conserved alanine- and
glycine-rich region of 16 residues as well  as a region centered on the second
cysteine involved in the disulfide bond.

-Consensus pattern: A-G-A-A-A-A-G-A-V-V-G-G-L-G-G-Y
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: E-x-[ED]-x-K-[LIVM](2)-x-[KR]-[LIVM](2)-x-[QE]-M-C-x(2)-
                    Q-Y
                    [C is involved in a disulfide bond]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: November 1997 / Text revised.

[ 1] Stahl N., Prusiner S.B.
     "Prions and prion proteins."
     FASEB J. 5:2799-2807(1991).
     PubMed=1916104
[ 2] Brunori M., Chiara Silvestrini M.C., Pocchiari M.
     "The scrapie agent and the prion hypothesis."
     Trends Biochem. Sci. 13:309-313(1988).
     PubMed=2908696
[ 3] Prusiner S.B.
     "Scrapie prions."
     Annu. Rev. Microbiol. 43:345-374(1989).
     PubMed=2572197; DOI=10.1146/annurev.mi.43.100189.002021

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